Mostly Biomathematics Lunchtime Seminar

Multistability and constitutive relations of cell motion on Fibronectin lanes

Speaker: Martin Falcke, Max Delbrück Center for Molecular Medicine and Dept. of Physics, Humboldt University, Berlin

Location: Warren Weaver Hall 1314

Date: Tuesday, October 4, 2022, 12:30 p.m.


Behnam Amiri1, Johannes C.J. Heyn3, Joachim O. Rädler3, and Martin Falcke1,2

1 Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert Rössle Str. 10, 13125 Berlin, Germany;
2 Dept. of Physics, Humboldt University, Newtonstr. 15, 12489 Berlin, Germany; 3 Ludwig-Maximilians-Universität München
(LMU), Fakultät für Physik, Geschwister-Scholl-Platz 1, 80539 München, Germany

Cell motility on flat substrates exhibits coexisting steady and oscillatory morphodynamics, the biphasic adhesion-velocity relation, and the universal correlation between velocity and persistence (UCSP) as phenomena common to many cell types and observed simultaneously. Their universality and concurrency suggest a unifying mechanism to exist causing all three of them. We search for such a mechanism by investigating a large ensemble of trajectories of MDA-MB-231 cells on Fibronectin lanes. We find cells with steady or oscillatory morphodynamics and either spread or moving. We observe apparently spontaneous transitions between the dynamic regimes, spread and moving motion states and direction reversals. We formulate a biophysical theory on the basis of the force balance at the leading edge, the noisy clutch of retrograde flow and a response function of friction and membrane drag to integrin signaling. The theory reproduces the experimental results with good quantitative agreement in a large Fibronectin density range. Analysis of the experiments with the biophysical model establishes a stick-slip oscillation mechanism, explains multistability of cell states and state transitions, and shows protrusion competition to cause direction reversal events, the statistics of which explains the UCSP. The model also explains cell behavior at Fibronectin steps and the adhesion-velocity relation. We suggest a mechanism, where signaling sets the cellular parameters for a multistable dynamic regime with steady or oscillatory morphodynamics, spread or moving motion states. These dynamics are driven by F-actin polymerization and shaped by the clutch mechanism of retrograde flow friction, protrusion competition via membrane tension and drag forces.